Radunovic Aleksandar, Annane Djillali, Rafiq Muhammad K, Brassington Ruth, Mustfa Naveed
Barts MND Centre, Royal London Hospital, Whitechapel, London, UK, E1 1BB.
Cochrane Database Syst Rev. 2017 Oct 6;10(10):CD004427. doi: 10.1002/14651858.CD004427.pub4.
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the most common cause of death, which usually occurs within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the second update of a review first published in 2009.
To assess the effects of mechanical ventilation (tracheostomy-assisted ventilation and non-invasive ventilation (NIV)) on survival, functional measures of disease progression, and quality of life in ALS, and to evaluate adverse events related to the intervention.
We searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL Plus, and AMED on 30 January 2017. We also searched two clinical trials registries for ongoing studies.
Randomised controlled trials (RCTs) and quasi-RCTs involving non-invasive or tracheostomy-assisted ventilation in participants with a clinical diagnosis of ALS, independent of the reported outcomes. We included comparisons with no intervention or the best standard care.
For the original review, four review authors independently selected studies for assessment. Two review authors reviewed searches for this update. All review authors independently extracted data from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from the included studies.
For the original Cochrane Review, the review authors identified two RCTs involving 54 participants with ALS receiving NIV. There were no new RCTs or quasi-RCTs at the first update. One new RCT was identified in the second update but was excluded for the reasons outlined below.Incomplete data were available for one published study comparing early and late initiation of NIV (13 participants). We contacted the trial authors, who were not able to provide the missing data. The conclusions of the review were therefore based on a single study of 41 participants comparing NIV with standard care. Lack of (or uncertain) blinding represented a risk of bias for participant- and clinician-assessed outcomes such as quality of life, but it was otherwise a well-conducted study with a low risk of bias.The study provided moderate-quality evidence that overall median survival was significantly different between the group treated with NIV and the standard care group. The median survival in the NIV group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% confidence interval 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, in the subgroup with normal to moderately impaired bulbar function (20 participants), median survival was 205 days longer (216 days in the NIV group versus 11 days in the standard care group, P = 0.0059), and quality of life measures were better than with standard care (low-quality evidence). In the participants with poor bulbar function (21 participants), NIV did not prolong survival or improve quality of life, although there was significant improvement in the mean symptoms domain of the Sleep Apnea Quality of Life Index by some measures. Neither trial reported clinical data on intervention-related adverse effects.
AUTHORS' CONCLUSIONS: Moderate-quality evidence from a single RCT of NIV in 41 participants suggests that it significantly prolongs survival, and low-quality evidence indicates that it improves or maintains quality of life in people with ALS. Survival and quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Adverse effects related to NIV should be systematically reported, as at present there is little information on this subject. More RCT evidence to support the use of NIV in ALS will be difficult to generate, as not offering NIV to the control group is no longer ethically justifiable. Future studies should examine the benefits of early intervention with NIV and establish the most appropriate timing for initiating NIV in order to obtain its maximum benefit. The effect of adding cough augmentation techniques to NIV also needs to be investigated in an RCT. Future studies should examine the health economics of NIV. Access to NIV remains restricted in many parts of the world, including Europe and North America. We need to understand the factors, personal and socioeconomic, that determine access to NIV.
肌萎缩侧索硬化症（ALS），也被称为运动神经元病，是一种致命的神经退行性疾病。神经肌肉呼吸衰竭是最常见的死因，通常在疾病发作后的两到五年内发生。通过机械通气支持呼吸功能可能会提高生存率和生活质量。这是首次发表于2009年的一篇综述的第二次更新。
评估机械通气（气管切开辅助通气和无创通气（NIV））对ALS患者生存率、疾病进展的功能指标以及生活质量的影响，并评估与干预相关的不良事件。
我们于2017年1月30日检索了Cochrane神经肌肉专业注册库、Cochrane对照试验中央注册库（CENTRAL）、MEDLINE、Embase、CINAHL Plus和AMED。我们还检索了两个临床试验注册库以查找正在进行的研究。
涉及临床诊断为ALS的参与者进行无创或气管切开辅助通气的随机对照试验（RCT）和半随机对照试验，与报告的结果无关。我们纳入了与无干预或最佳标准治疗的比较。
对于原始综述，四位综述作者独立选择研究进行评估。两位综述作者审查了本次更新的检索结果。所有综述作者独立从选定研究的全文中提取数据，并评估符合纳入标准的研究中的偏倚风险。我们尽可能尝试获取缺失数据。我们计划从纳入研究中收集不良事件数据。
对于原始的Cochrane综述，综述作者识别出两项RCT，涉及54名接受NIV的ALS参与者。第一次更新时没有新的RCT或半随机对照试验。在第二次更新中识别出一项新RCT，但因以下原因被排除。一项比较NIV早期和晚期启动的已发表研究（1个参与者）的数据不完整。我们联系了试验作者，他们无法提供缺失数据。因此，该综述的结论基于一项对41名参与者的单一研究，该研究比较了NIV与标准治疗。对于参与者和临床医生评估的结果，如生活质量，缺乏（或不确定）盲法代表了偏倚风险，但除此之外，这是一项实施良好且偏倚风险较低的研究。该研究提供了中等质量的证据，表明接受NIV治疗的组与标准治疗组之间的总体中位生存期存在显著差异。NIV组的中位生存期长48天（NIV组为219天，标准治疗组为171天（估计95%置信区间为12至91天，P = 0.0062））。这种生存获益伴随着生活质量的提高。在亚组分析中，在延髓功能正常至中度受损的亚组（20名参与者）中，中位生存期长205天（NIV组为216天，标准治疗组为11天，P = 0.0059），生活质量指标优于标准治疗（低质量证据）。在延髓功能较差的参与者（21名参与者）中，NIV并未延长生存期或改善生活质量，尽管通过某些测量方法，睡眠呼吸暂停生活质量指数的平均症状领域有显著改善。两项试验均未报告与干预相关的不良反应的临床数据。
一项对41名参与者进行的NIV单一RCT的中等质量证据表明，它能显著延长生存期，低质量证据表明它能改善或维持ALS患者的生活质量。延髓功能较好的亚组患者的生存期和生活质量有显著改善，但延髓严重受损的患者则不然。应系统报告与NIV相关的不良反应，因为目前关于这一主题的信息很少。由于不给对照组提供NIV在伦理上不再合理，因此很难获得更多支持在ALS中使用NIV的RCT证据。未来的研究应研究NIV早期干预的益处，并确定启动NIV的最合适时机以获得最大益处。还需要在RCT中研究在NIV中添加咳嗽增强技术的效果。未来的研究应研究NIV的卫生经济学。在世界许多地区，包括欧洲和北美，NIV的获取仍然受限。我们需要了解决定NIV获取的个人和社会经济因素。
